MON-LB053 Involvement of Stromal Age in Breasts Cancer Endocrine Response

Abstract

Adipose tissue is a known endocrine organ, source of hormones and paracrine factors. In disease states such as cancer, endocrine and paracrine signals from adipose tissue contributes to cancer progression and drug resistance. Both adipocytes and adipose derived stem cells (ASC) have been identified as a source of paracrine factors such as stromal derived factor (SDF1), insulin-like growth factor (IGF1), and leptin (LEP). These signaling molecules enhance breast cancer progression and regulate resistance to endocrine therapies in estrogen receptor (ER) positive breast cancer. Young individuals diagnosed with luminal ER+ breast cancer have an observed increase in resistance to endocrine therapies such as tamoxifen. Currently, the effects of stromal age and its contribution to endocrine resistance is not well known. In this study, we aimed to evaluatethe effects of ASC donor age on endocrine resistance in ER+ breast cancer. Evaluation of RNA sequencing of clinical breast cancer data obtained from The Cancer Genome Atlas (TCGA) of ER+ breast cancer tumors from young individuals (<40 years old) and aged individuals (>65 years old) demonstrated that genes enriched in young (<40 years old) ER+ breast cancer compared to aged ER+ (>70 years old) demonstrated increased cytokines and regulators of endocrine resistance (IL-12B, IL-20, IL-11, FGF1, PDGFB, TGFB3, TGFA, SDF1, IGF1, TGFB2, CTGF). Through a series of condition media-based experiments we demonstrate that ASC donor age is a contributing factor to endocrine resistance. Our results showed that secreted factors from young ASCs enhanced estrogen signaling in the MCF-7 ER+ breast cancer cell line compared to MCF-7 cells treated with secreted factors from aged ASCs. This was evident through the observed increase in ER regulated genes (PGR and SDF1) in MCF-7 cells stimulated with young ASC CM compared to aged ASC CM. Additionally, western blots showed increased activation of p-ER ser167 in the MCF-7 cell line treated with young ASC secreted factors not aged secreted factors. These results are important in understanding the mechanisms of endocrine resistance in young breast cancer patients, as well as identifying a unique molecular composition of young (<40 years of age) breast cancer patients compared to aged (>65 years of age). Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.